Anticoagulants are widely used therapeutic agents in the treatment of cardiovascular disease. During the 30 years of their therapeutic use, coumarin anticoagulants have been found to interact with a number of other drugs. Little information, however, is currently available concerning drug interactions at the gastrointestinal absorption level. Sine maintenance of a precise, stable level of coagulability is critical in the coumarin anticoagulated patient, knowledge of potential absorption interactions when considering institution of additional drug therapy is most important and must be gained through systematic investigation. Preliminary work in our laboratory has revealed a 21% decrease in oral bishydroxycoumarin absorption in rats after pretreatment with heptabarbital. This is in agreement with a previous report in the literature involving studies in human subjects. The proposed project is designed to investigate absorption interaction between bishydroxycoumarin and heptabarbital, and will provide information concerning absorption interactions of anticoagulants with other barbiturates and other classes of pharmacologic agents which may be administered concurrently in drug therapy. In situ and in vivo techniques will be utilized to examine the absorption profile of coumarin anticoagulants in the presence of other drugs. The optimum site for coumarin absorption will be examined, as will be potential mechanisms by which other drugs may modify coumarin absorption. Mechanisms to be investigated include among others, effects on gastric emptying and intestinal transient, alterations in biliary excretion and entero-hepatic cycling. The relationship of alterations in gastrointestinal absorption of anticoagulants to modification of their pharmacologic effect will also be established.